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Journal of
ENT MASTERCLASS®
Year Book 2009Volume 2 Number 1
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For further information please email:
ukfocus@its.jnj.com
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Chairman’s Comment and Editorial Board: 3
Editorial 4
HPV as an Aetiological and Prognostic Factor in H&N Cancer 5 Lisa Licitra, Laura D Locati, C Bergamini, Paolo Bossi
Robotic Surgery for Head and Neck Tumors 9Gregory S. Weinstein, MD, Fernando Danelon Leonhardt, MD, MSc, Bert W. O´Malley Jr,
MD, Harry Quon, M.D.
Head and Neck Melanoma: Current Surgical Practices 13 Zvonimir L. Milas, MD and Randal S. Weber, MD
Sentinel Node in Head and Neck Cancer 17Susanne Wiegand, Jochen A. Werner
Management of Medullary Thyroid Carcinoma 22 BJ Harrison MS FRCS
Current surgical management of unilateral vocal fold paralysis 26 Declan Costello, MA, MBBS, FRCS (ORL-HNS), Meredydd Harries, FRCS, MSc
Infections and Neoplasms of the Parapharyngeal Space 30 Patrick J Bradley, MBA, FRCS
Principles of Radiotherapy in Cancer of the Head and Neck 38
Bhide S, Newbold K, Harrington KJ, Nutting CM,
The Aging Voice 44 Lindsey Clemson Arviso MD, Michael M Johns III, MD
Early stage glottic squamous cell carcinoma: radiotherapy or endoscopic 50surgery current practice and controversies Jarrod J Homer MD FRCS
Granulomatous Disease in the Nose 56 JW Rainsbury MRCS, DW Skinner FRCS
Endoscopic Lacrimal surgery - how and does it work? 62 Neil C-W Tan MRCS, DO-HNS, Peter-John Wormald MD, FRCS, FRACS, Salil B Nair FRCS
Olfactory dysfunction – Assessment and management 68 Emma JM McNeill FRCS (ORL-HNS) Sean Carrie FRCS (ORL-HNS)
Facial pain in a Rhinology Clinic 74 Mr Shahzada Ahmed BSc (Hons) FRCS (ORL-HNS,) Professor NS Jones FRCS
Outcome in Functional Endoscopic Sinus Surgery (FESS) for Rhinosinusitis 78 Pernilla Sahlstrand-Johnson MD, Christian von Buchwald MD, PhD
JOURNAL OF ENT MASTERCLASS ®
Volume 2 Issue 1 December 2009
Contents
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Paediatric Cochlear Implantation: Is one as good as two? 84 John Murphy FRCS (ORL-HNS), Andrew H Marshall FRCS (ORL-HNS),
Current Concepts in Juvenile Nasopharyngeal Angiofbroma 88 Henry B Nongrum MS, Alok Thakar MS, FRCSEd, Gaurav Gupta MS, Siddharth Datta Gupta MD
Pediatric Drooling 96 Dennis Kitsko DO, Deepak Mehta MD FRCS
Auditory brainstem implantation: indications and outcomes 101Shakeel R. Saeed MBBS, MD, FRCS (ORL)
Noise-induced hearing loss 107 James Mitchell MBBS PgDL MRCSEd DOHNS, Andrew McCombe MD FRCS
Management of Otosclerosis: Current Opinions 112 Acharya AN MRCS, Oates J FRCS
Evidence Based Management of Bell’s Palsy 119 N Mehta MBBS, MRCS, DOHNS, S Ifeacho MBChB, MRCS, DOHNS,
A Narula MA FRCS FRCS (Ed)
Autoimmune Inner Ear Disease (AIED) 125Simon A. McKean MB, MRCS, DOHNS, S. S. Musheer Hussain MB, M.Sc.(Manc) FRCS, FRCS (Ed)
Evaluation of the Dizzy Patient 128Courtney C. J. Voelker, M.D., D.Phil., Joel A. Goebel, M.D., F.A.C.S
Malignant Otitis Externa 137 Jonathan Bernstein MB ChB MRCS(Eng) DOHNS, N Julian Holland MSc FRCS
ENT Masterclass® Calender 2010-2011 144
Disclaimer: The individual authors have responsibility for the integrity of the content of the manuscripts.
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3
Welcome to Volume 2 Issue 1 of Journal of ENT Masterclass ® !
The ENT Masterclass has established itself as a well-recognized training event.
Each year for the past 2 years the courses have expanded to not only includedoctor or medical tuition, but also nursing staff. There are currently four fixed
annual events and during 2009 these were; January the 5th Annual NationalENT Masterclass, May the 2nd Tracheostomy Masterclass, June the2nd Thyroid and Salivary Masterclass, and September the 3rd National
Nursing Masterclass. Each of these Masterclass’ are a success not only toShahed Quraishi, the Founder and Organiser of the Masterclass concept, butthanks also go to the dedication of the Faculty in giving-up their valuable time,
the support of Doncaster & Bassetlaw NHS Foundation Trust, sponsorshipand the volunteers who help with the logistics allowing to keep these coursescompletely free of cost to the attendees.
An extension or expansion of ENT Masterclass was the launch of TheJournal of ENT Masterclass in January 2009 with 21 review articles on
current ENT topics from national and international authors. This year,
Volume 2 Issue 1, we have continued along the same lines expanding thecontents with 26 invited articles, with topics divided into Head and Neck,
Nose and Sinuses, Pediatrics and Otology and Neuro-otology. Feed-backhad suggested that a contribution from International Experts was a “novel
idea”, this issue is fortunate to have increased these contributions from2 to 10, which will probably be our “ceiling” for future Journal Issues. Againwe are indebted to the many “locals” who have willingly contributed, some
for the second time, to the Journal’s success.
During the 5th National ENT Masterclass Mr Barney Harrison, President-Elect
of the British Association of Endocrine and Thyroid Surgeons, ConsultantSurgeon from Sheffield gave the Second ENT Masterclass Lecture 2008 on“Evaluation and Management of Thyroid Nodules”. His lecture was given with
eloquence with his usual confidence, didactic and demonstrating his life-timeexperience with the management of thyroid diseases.
The Editorial Board has undergone change, with the loss of ProfessorA Wright and Mr David Pothier. We would like to thank them for their helpand support. The Board has been expanded to reflect the wider curriculum,
to reflect the distribution and internationalisation of The Journal. Acceptingthe invitation and coming “on board” are Mr Alec Blayney, Ireland, ProfessorGreg Weinstein, USA, Professor Simon Carney, Australia, Mr Derek Skinner,
Shrewsbury, Mr Ken McKenzie, Glasgow.
Again, The Journal welcomes suggestions and comments on how to better
the Masterclass concept! Most current sources and information can beobtained on the website, as well making direct contact to the Editor and theChairman of the Editorial Board!
The Journal and Masterclass continue to thank each and everybody for theirinvolvement, for their continued support and remain in your debt!
Professor Patrick J Bradley, MBA, FRCSChairman of the Editorial Board,
Journal of ENT Masterclass,Nottingham.
E-mail: pjbradley@zoo.co.uk
November 2009.
JOURNAL OF ENT MASTERCLASS ®
Editor:Mr. M S QuraishiFRCS (Eng) FRCS (ORL, H&N) Consultant ENT Surgeon Hon Senior Lecturer in SurgicalOncologyDoncaster Royal Infirmary Doncaster, UK E-mail:shquraishi@entmasterclass.com
Chairman Editorial Board:Prof. P J Bradley MBA FRCSConsultant ENT Surgeon Head & Neck Oncologist University Hospital Nottingham, UK E-mail: pjbradley@zoo.co.uk
Editorial Board:
Mr A Blayney (Eire)Mr K MacKenzie (UK)Prof A Narula (UK)Prof S R Saeed (UK)Mr A Sama (UK)Mr R Simo (UK)Mr D W Skinner(UK)Prof G S Weinstein (USA)
ENT Masterclass ® ,106 Nottingham Road,Ravenshead,NottinghamNG15 9HLEngland
www.entmasterclass.com
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J O U R N A L O F E N T M A S T E R C L A S S ®
Following a series of high profile scandals involvingindependent reports (Bristol, Ledward, Alder Hey) thepolitical climate in Britain changed and the medicalprofession was warned by the Chief Medical Officer that
some kind of regular ‘MoT’ certificate would be required.These scandals were like manna from heaven for politicianswho were keen to take doctors down a peg or two.However, his initial proposals were thrown into disarraywhen Dame Janet Smith severely criticized these proposalsin her final report into the activities of the mass murdererHarold Shipman. Many observers feel she went wellbeyond her brief in making these comments but the CMOwas forced to go back to the drawing board. This then ledto a White paper in 2007: Trust Assurance and Safety.
This White paper introduced two concepts: relicensing andrecertification, together called revalidation. All doctors onthe GMC register would now require a formal Licence toPractise and this has in fact already been introduced (Nov2009) and that every five years all doctors would be subjectto revalidation of this licence via relicensing.
In addition to relicensing, all doctors on the Specialistregister would also have to be recertified as specialistsevery 5 years. In practice the two parts to revalidationwould run as one. The medical Royal Colleges have beencharged with describing the standards that specialistsshould meet and the RCS has worked closely with ENT-UKto set these standards for us. Maurice Hawthorn has beenleading on this for our specialty.
“Recertification, like relicensure, will be a positiveaffirmation of the doctor’s entitlement to practise, not
simply an absence of concerns.” The stated purpose is thus to further ensure patientsafety and to facilitate improvement in clinical practice (i.e.to stop a future Shipman).
How revalidation can be achieved is also a source ofmassive effort. It is expected that specialists will have toundergo a more robust annual appraisal (now known asstrengthened appraisal) every year and that the 5 yearlyrevalidation event will be a formal review of the preceding5 years of strengthened appraisals. It therefore follows thatwe will all have to provide a great deal of data about ourpractice in a number of different domains. These include:
• outcomes data
• evidence of participation in any relevant national audits• attendance at M&M and MDT meetings• CPD which will have to be carefully logged
All doctors must be the subject of a multi-source feedbackexercise (often known as 360 degree assessment) and,where appropriate, patient surveys. However, despitesome pilot work, this process is not yet validated as ameans of assessing professionals such as doctors. DrShipman would have received glowing reports from hispatients! It therefore follows that such evidence cannot beconsidered alone but as part of a wider assessment.
Much of this will come as an unpleasant surprise toestablished consultants but younger colleagues (andtrainees) will be quite familiar with this approach. RCSand RCS Ed are currently developing electronic portals to
help Fellows collect and store this information.The entire process is the statutory responsibility of theGMC not the DH and so crosses all four home nations.The Deptartment of Health in England . has set up aRevalidation Support Team to support the process but ofcourse each health department may yet take a differentview in each nation. Currently the start date forrevalidation has moved from 2010 to mid 2011. As thereare over 60 different specialties in medicine a staggeredstart is expected - taking perhaps 5 years. So by around2016 all specialists will be embroiled in this process.However, no financial modelling has taken place and sono realistic estimate of the costs can be made.
Employers will be key to the annual process and yet theyhave not been closely involved in developing these ideas.In addition, the role of the Colleges in providing qualityassurance of the process has not been defined. All ENT-UK members must expect a fair and transparent process- especially if problems are identified which mightthreaten your place on the specialist register. I havegrave concerns that appraisal inside a Trust often focuseson how well you are meeting targets etc. But this is aseparate issue from the key one of whether you are fit toremain on the specialist register.
A further problem arises in the case of those carrying outindependent (private) practice. Currently appraisal issupposed to be of your whole practice. Often it is not. Underrevalidation this will have to change and private hospitals willbe obliged to involve themselves in the process.
As I write this there are expectations that the UK will havea new Government in 2010. They are expected to facesevere financial problems following on from the bankingcrisis of 2008/9 and I would not be too surprised if thetimetable for introducing revalidation slips further. Themost likely side effect of this legislation is that the hugeincrease in bureaucracy will encourage many specialiststo take early retirement in the years leading to 2016.While this will open up job opportunities for trainees, theloss of a huge swathe of experienced specialists aged 60and over will be a great loss for the Health Service and asad unwanted consequence. The Law of UnintendedConsequences still applies.
And as any medical director will tell you privately, this processwill not prevent another Shipman: which of course continuesto leave a deficit in the regulation of doctors in the UK.
Professor Tony Narula MA FRCS FRCS Ed RCS Lead for RevalidationENT Consultant, Imperial HealthcareLondon W2
Editorial: Revalidation
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Y E A R B O O K 2 0 0 9 V O L U M E 2 N U M B E R 1
IntroductionHead and neck squamous cell carcinomas (HNSCC) arise
from the mucosa of the upper digestive tract. Taken
together they have an annual incidence, world-standardised,
of 25/100,000 and 4/100,00 in European men and women,
respectively, with significant variations among the
European regions1.
Head and neck cancers are subcategorized according to
their site of origin due to different etiology, managementand outcome. Strong carcinogenic and epidemiologic
evidences support an etiopathogenetic role of tobacco and
alcohol; in fact, about 90% of cases is due to them.
Recently, oncogenic human papilloma viruses (HPV) have
been associated with a subset of HNSCC2. HPV DNA is
present in the tumor, more frequently in those arising in
the oropharynx, although it has rarely been detected also
in oral cavity, larynx and hyopharynx. HPV positive
testing varies across countries in different series, ranging
from 20 to 72%, depending also on the detection
techniques3. In general, more recent studies tend to report
an increase in HPV tumor positivity4
. Moreover, a relativerising number of oropharyngeal cancer, together with a
declining incidence of oral cavity, larynx and
hypopharyngeal cancer, has been reported in the United
States and Europe5-8. In Sweden the proportion of HPV
positive tonsillar cancers had significantly increased since
1970s with 93% of positivity in 2006-2007, thus suggesting
a virus induced carcinoma epidemic with the virus
presence in virtually all tonsillar cancers, similar to
cervical tumor9.
HPV as aetiological factorSimilarly to cervical cancer, high risk sexual behaviours,
exposure and infection have been correlated with
oropharyngeal cancer in a case control study10.
Sexual behaviours increasing the risk of developing HPV
oropharyngeal associated cancer have been defined as
having more than 6 lifetime vaginal partners, having oral
sex, anal sex, never or rarely using condoms and having
sexual partners with a history of HPV related cancers.
When just infection is taken into account, then oral sex
and open mouth kissing are associated with an increased
probability of oral HPV infection. The infection prevalence
in a college aged men’s cohort is 3%, while that in a non
selected general outpatient clinic population is 5%11.
In the HIV positive population HPV related cancers are
statistically significantly higher than in the general population12.
However, in contrast to the high risk of other HPV associated
cancers, the risk to develop oropharyngeal cancer was only
modestly increased and, paradoxically, the onset oforopharyngeal tumors was more frequently in AIDS patients
with a relatively higher CD4 T - cell count. Nevertheless, HIV
positive patients treated with active antiretroviral therapy are
expected to live longer, thus increasing their risk to develop
HPV oropharyngeal cancer13.
Markers of exposure and infection, such as HPV16 viral
capsid (L1) serologic status, HPV 16 oral infection, any
HPV oral infection, E6 and E7 HPV 16 oncogenes
HPV as an Aetiological and PrognosticFactor in H&N CancerLisa Licitra, Laura D Locati, C Bergamini, Paolo Bossi
Head and Neck Medical Oncology Unit,
Fondazione IRCCS “Istituto Nazionale dei Tumori” in Milan, Italy
Corresponding author: Lisa Licitra, MD
Head and Neck Medical oncology Unit
Fondazione IRCCS “Istituto nazionale dei Tumori”
Via venezian 1
20133 Milano - Italy
Phone: +39 02 23903352
Fax: +39 02 23903353
e.mail: lisa.licitra@istitutotumori.mi.it
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serologic status, have been found to be significantly
associated with the risk of developing an oropharyngeal
cancer. This risk seems to be independent of alcohol and
tobacco use. In particular, in HPV16 seropositive patients
the risk was not affected by alcohol and smoking increasing
consumption14. On the contrary, in seronegative patients
this risk significantly increases with increased alcoholintake and smoking. In general, HPV16 seropositivity was
associated with a 10-fold increased risk of pharyngeal
cancer after adjusting for alcohol and tobacco use. Among
patients drinking less than 3 drinks/week or among never–
smoker patients, HPV seropositivity was associated with a
30-fold increased risk of developing a pharyngeal cancer.
Interestingly, smoking habits can have a modulating
impact on the favourable prognostic outcome of HPV
positive patients, as it has been recently demonstrated15.
HPV oral infection through oral rinse serial analysis could
be also exploited to detect not only subjects at risk to
develop tumors, but also to provide earlier evidence of
tumor recurrence after therapy. It has been shown that in
the majority of cases the HPV variant sequence is of the
same type of the index tumor. Its presence has been shown
for as long as 5 years. Moreover, the prevalence of HR
HPV infections other than HPV 16 is common in patients
with HPV16 positive tumors before and after treatment16.
In some rinses a different HPV variant was detected,
suggesting the possibility of a different infection. According
to the present study no correlation was found between
HPV persistency and development of tumor recurrence
and/or second tumors. However, numbers were small andfollow up still brief to conclude that this marker is useless
in the clinic. In another small case series the presence of
HPV16 E6 and E7 in convalescent salivary rinses turned
out to predict tumor recurrence or metastasis17, Contrary
to cervical infection, the time course of oral infections is
still unknown. Similarly to cervical cancer, genetic
variants, such as HLA class and chemokines may influence
viral oral clearance, but individual predisposition of HPV
oral infection has to be further investigated. Interestingly,
familial clustering of HPV related cancers, including
oropharyngeal tumor site, has been described by the
Swedish data base. The study could not allow to understandwhether the observation was due to shared environmental
or genetic factors18. Genetic susceptibility of developing
HPV related head and neck cancers has been reported to
be represented by p53 codon 72 polymorphism and with a
variant vitamin C transpoter SLC23A219,20.
A biological causal relationship has been postulated on the
basis of the integration of HPV DNA, particularly HPV 16
and the expression of oncogenic viral genes, such as E6
and E7, high viral load that has been consistently found in
oropharyngeal carcinomas21. Indeed, this has been less
rigorously demonstrated for other head and neck subsites.
It is possible that oropharynx offers a facilitated access to
the mucosal basal cell layer in the tonsillar crypts,
similarly to what happens in the cervical transformation
zone. HPV16 is the most common type identified in allhead and neck cancers, in less than 10% of cases other
high risk types (18, 31, 33 and 35) have been detected.
Corollary evidence is provided by the presence of
antibodies directed against HPV16 E6 and E7 oncoproteins,
HPV seropositivity and oral HPV in patients with HPV
positive oropharyngeal cancers.
Molecular alterations, including those occurring at p53,
cyclin D1, p16, pRB in tumors induced by HPV are
tipically different as compared to HPV negative squamous
head and neck carcinoma, supporting the existence of two
distinct carcinogenetic pathways. Other markers, such as
EGFR expression, have been found to be inversely
correlated with HPV positivity22. Interestingly, hypoxia
markers were not found to be correlated with HPV
positivity, thus suggesting that this may not be the
mechanism responsible of radiosensitivity of HPV positive
tumors (see below)23.
Genetic patterns are also different in head and neck cancer,
either containing or lacking transcriptionally active HPV.
HPV positive tumors are characterised by occasional
chromosomal loss, on the contrary in HPV negative tumor
cells there are gross chromosomal deletions tipically seen
in the early phase of tumor development24,25. In a recentstudy chromosomal alterations among HPV positive
cancer cells of cervical and oropharyngeal origin has been
shown to be organ site specific26.
HPV as prognostic factorSurvival of patients with HPV head and neck tumors has
been analysed in a study metanalysis, which showed a
lower risk of dying (HR 0.85) and a lower risk of
recurrence (HR 0.62) in HPV positive tumors. Interestingly,
this seems to be a site specific effect since, for example,
OS was not different among HPV positive oropharyngeal
versus non oropharyngeal tumors27
. Different reasons offavourable survival outcome have been hypothesized to be
intact apoptotic machinery in response to radiation and
possibly chemotherapy, absence of field cancerization and
immune system activation by viral specific tumor
associated antigens. They are all based on the recognition
of a separate and specific biologic profile of HPV positive
tumors that justify its distinct behaviour15,21,28. Interestingly,
a better outcome has been seen for patients undergoing
primarily surgery for oropharyngeal cancer, as well
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suggesting the possibility of a less aggressive tumor29.
This observation is also corroborated by the reduced
incidence of distant metastases that were observed in a
retrospective evaluation of patients enrolled in a phase III
study conducted in Italy on oropahryngeal cancer30.
Prospective studies including HPV positive tumors alsoshowed a statistical improvement of response rates, as
well as organ preservation data, disease free survival and
better survival31,32. One of these studies pointed out that
response rate to induction chemotherapy correlates with
HPV16 gene copies quantified in the single tumor. The
same observation was done by considering p16 tumor
staining that is now recognised as an effective and reliable
marker of HPV positivity in head and neck cancer33.
Indeed, p16 immunohistochemical expression has been
strongly correlated with in situ hybridisation and HPV
gene expression through PCR analysis15,34.
Smoke status, categorised as never smoker, past smoker
and current smoker or per pack/year, has been associated
with the outcome of patients with HPV positive oropharyngeal
cancer15,33. For some still unclear reasons current and past
smoking negatively affects the cure probability of HPV
positive tumors. An inverse correlation between EGFR
expression and smoking has been also observed, possibly
suggesting a role of EGFR pathway in determining prognosis.
To date studies that correlate HPV positivity and tumor
response to EGFR inhibitors have not been reported. Given
the absence of any correlation between EGFR status and
tumor response to cetuximab35, if HPV positivity is associated
with a better outcome with EGFR inhibitors, then the reasonshould not be attributed to the more preserved EGFR status
correlated with tumor HPV infection.
In conclusion, HPV positive tumor patients display an
epidemiologic, biological and outcome profile that has
paved the way for considering it a separate tumor entity
which deserves special attention and also special care in
the future. The research strategies for HPV positive tumor
are now concentrated in studying prospectively whether a
treatment de-escalation to avoid unnecessary acute and
late toxicity is foreseeable, for example by reducing
radiation both in terms of total dose and irradiationvolumes or by skipping concomitant chemotherapy or by
using biological therapy instead of chemotherapy. By
separating those patients clinical research in head and
neck cancer will have to focus on more aggressive tumors,
for which biology will have a prominent role in designing
future studies.
It has to be recognised that HPV infection is sexually
transmitted and any high-risk sexual behaviour is associated
with oral HPV infection10. In this context strategies of
primary prevention to reduce high-risk sexual behaviours
among adolescents and the young population must be
considered in public health. Vaccination of adolescents
and young adults to hasten the reduction of HPV-16
prevalence has been claimed although its efficacy at
population level has not yet been demonstrated.
AcknowledgmentAuthors have no financial conflict of interest to be
disclosed.
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17. Chuang AY, Chuang TC, Chang S, et al. Presence of HPV DNA inconvalescent salivary rinses is an adverse prognostic marker in headand neck squamous cell carcinoma. Oral Oncol 2008;44:915-919.
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vitamin C transporter, SLC23A2, modifies the risk of HPV16-associated head and neck cancer. Carcinogenesis 2009;30:977-981.
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22. Perrone F, Suardi S, Pastore E, et al. Molecular and cytogenetic subgroups of oropharyngeal squamous cell carcinoma. Clin CancerRes 2006;12:6643-6651.
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24. Braakhuis BJ, Snijders PJ, Keune WJ, et al. Genetic patterns in headand neck cancers that contain or lack transcriptionally active
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HPV-related and unrelated oropharyngeal carcinoma and their prognostic implications. Clin Cancer Res 2009;15:1779-1786.
26. Wilting SM, Smeets SJ, Snijders PJ, et al. Genomic profilingidentifies common HPV-associated chromosomal alterations in squamous cell carcinomas of cervix and head and neck. BMC MedGenomics 2009;2:32.:32.
27. Ragin CC, Taioli E. Survival of squamous cell carcinoma of the headand neck in relation to human papillomavirus infection: review andmeta-analysis. Int J Cancer 2007;121:1813-1820.
28. Lassen P, Eriksen JG, Hamilton-Dutoit S, et al. Effect of HPV-associated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck. J ClinOncol 2009; 27 (12) :1992-1998.
29. Licitra L, Perrone F, Bossi P, et al. High-risk human papillomavirus
affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma. J Clin Oncol 2006; 24 (36):5630-5636.30. Fallai C, Perrone F, Licitra L, et al. Oropharyngeal Squamous Cell
Carcinoma Treated with Radiotherapy or Radiochemotherapy: Prognostic Role of TP53 and HPV Status. Int J Radiat Oncol BiolPhys 2009 (Abstracted ahead of publication)
31. Fakhry C, Westra WH, Li S, et al. Improved survival of patients withhuman papillomavirus-positive head and neck squamous cellcarcinoma in a prospective clinical trial. J Natl Cancer Inst2008;100 (4):261-269.
32. Worden FP, Kumar B, Lee JS, et al. Chemoselection as a strategy fororgan preservation in advanced oropharynx cancer: response and survival positively associated with HPV16 copy number. J ClinOncol 2008;26:3138-3146.
33. Kumar B, Cordell KG, Lee JS, et al. EGFR, p16, HPV Titer, Bcl-xLand p53, sex, and smoking as indicators of response to therapy and survival in oropharyngeal cancer. J Clin Oncol 2008;26:3128-3137.
34. Rischin D, Young R, Fisher R, et al. Prognostic significance of HPVand p16 status in patients with oropharyngeal cancer treated on alarge international phase III trial. J Clin Oncol 2009;27, No.15S:302s.
35. Licitra L, Rolland F, Bokemeyer C, et al. Biomarker potential of EGFR gene copy number by FISH in the phase III EXTREME study: Platinum-based CT plus cetuximab in first-line R/M SCCHN. J ClinOncol 2009;27, No. 15S:302s.
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Abstract
Minimally invasive surgery has been increasing in multiple
specialties as a means of reducing patient morbidity and
mortality; the surgical robot has add three-dimensional
visualization and significant technical advantages to these
approaches. Transoral Robotic Surgery (TORS) in Head
and Neck area presented major advances in neoplasms of
the larynx and pharynx, with clinical trials assessing large
series of patients with adequate follow-up for oncological,
morbidity and mortality results. Preclinical studies have
also demonstrated the feasibility of TORS in areas as the
skull base, nasopharynx, parapharyngeal space, and neck
surgery. In some anatomic sites it may also shift the
paradigm away from non-surgical approaches and back to
primary surgery.
Key WordsRobotic, minimally invasive surgery, transoral robotic
surgery, head and neck cancer
IntroductionMinimally invasive surgery has been increasing in multiple
specialties as a means of reducing patient morbidity and
mortality. The commercially available da Vinci surgical
robot (Intutive Surgical,Inc, Sunnyvale, CA, USA)
provides three-dimensional visualization and significant
technical advantages, allowing procedures to be performed
through a minimally invasive route, diminishing surgeon
tremor and fatigue. Since the introduction of the surgical
robot in the 1990’s, robot-assisted cardiac, gynecologic,
pediatric and urologic procedures have become widely
accepted internationally. In urologic surgery, approximately
60% of the patients underwent radical robot assisted
radical prostatectomy in the United States in 20071. Head
and neck tumors fequently requires a transcervical
approach, and sometimes jaw-splitting, and may result in
poor cosmesis and dysfunctional speech and swallowing2.
Experimental studies using canine and cadaver models
demonstrated the technical feasibility of transoral robotic
surgery (TORS)3,4. Complimentary studies in patients
have demonstrated both the feasibility and the safety of
robot-assisted resection of upper aerodigestive tract
neoplasms, with limited surgical morbidity, reduced
hospitalization, and enhanced visualization over traditional
techniques5-7.
The Robotic SystemThe da Vinci Surgical Robot (Intuitive Surgical, Inc.,
Sunnyvale, CA) is made up of three primary components:
a surgical cart, a vision cart, and a surgeon's console
(Figure 1). The surgical cart is equipped with a robotic
manipulator and three mounted arms: one arm holds thecamera and the other two hold 5 mm or 8-mm
instruments(Figure 2) . The vision cart is equipped with
two three-chip cameras mounted within one integrated,
three-dimensional 12-mm stereoscopic endoscope with
two separate optical channels. The surgeon's console,
positioned a distance ( approximately 5 to 10 feet) from
the patient acts as an operating microscope, displaying
stereoscopic images obtained by the double endoscopic
cameras. At this console the surgeon controls the instrument
Robotic Surgery For Head And Neck TumorsGregory S. Weinstein, MD+, Fernando Danelon Leonhardt, MD, MSc**, Bert W. O´Malley Jr, MD+,
Harry Quon, M.D.++
+Department of Otorhinolaryngology: Head and Neck Surgery
University of Pennsylvania, Philadelphia, Pennsylvania, USA**Department of Otorhinolaryngology Head and Neck Surgery
Federal University of São Paulo, São Paulo, Brazil
++Department of Radiation Oncology
University of Pennsylvania, Philadelphia, Pennsylvania, USA
Corresponding Author
Gregory S. Weinstein, MD
Professor and Vice Chair
3400 Spruce St, 5 Ravdin/Silverstein, Philadelphia, PA 19104-4283
Phone: 215 3495390
Fax: 215 3495977
E-mail: gregory.weinstein@uphs.upenn.edu
The authors regard themselves as joint first authors
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arms and camera by maneuvering the robotic manipulators(Figure 3). Instrument tips are electronically aligned with
the instrument controllers to provide optimal eye-hand
orientation and natural operative capability. The robotic
arm is designed to hold surgical instruments that are
"wristed" and are completely controlled by the surgeon's
movement of the handles in the console and precisely
duplicate the motion of the surgeons hands while providing
motion scaling of the hand movements to accomadate for
the miniaturized instruments on the robotic cart (Figure 4).
The advantages of this system are: realistic 3-D imaging,
motion scaling, 6° of motion around the "wrists" of the
instruments and physiologic tremor filtration.
Robotic-Assisted SurgeriesTo the date, several uses for the robot-assisted surgery in
Head and Neck area have been described both in preclinical
set-ups with animals and cadaveric models, and on clinical
trials. Major advances occurred in neoplasms of the
oropharynx and larynx, with clinical trials assessing large
series of patients with adequate follow-up for oncologicaland morbidity and mortality results. Although preclinical
studies have demonstrated the feasibility of TORS in areas
as the skull base, nasopharynx, parapharyngeal space,
have, there remains a lack of large number of patients and
late follow-up in clinical trials of these anatomic sites.
OropharynxOropharynx neoplasms comprises primarily of tonsil and
tongue base malignancies. Lately, there have been
increasing reports of the use of primary radiation or
combined chemotherapy and radiation for tongue base and
tonsil neoplasms 8. The key factor driving this movement
away from primary surgery was the reported morbidity ofsuch surgical procedures9. Cervical incisions and
dissections with mandibulotomy or pharyngotomy were
typically required to remove base of tongue neoplasms
even in the early stages10. These approaches left the
Figure 1 – da Vinci surgical robot (Intutive Surgical,Inc,Sunnyvale, CA, USA) Robotic Console.
Figure 2 – da Vinci surgical robot (Intutive Surgical,Inc,Sunnyvale, CA, USA) Robotic bedside cart.
Figure 3 – da Vinci surgical robot (Intutive Surgical,Inc,Sunnyvale, CA, USA) Robotic Console manipulators.
Figure 4 - Surgeon’s view of instruments via the viewing porton the da Vinci surgical robot (Intutive Surgical,Inc,Sunnyvale, CA, USA) Robotic Console.
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patient with various levels of significant speech and
swallowing dysfunction as well as cosmetic deformity
depending on the size and location of the tumor and extent
of resection. TORS eliminates the need for mandibulotomy
with a lip split or visor flap or transpharyngeal approaches
that adversely affect mastication, swallowing and speech
function, and cosmesis. In addition, we believe that TORStongue base resections and radical tonsillectomies can be
performed safely without tracheostomy, which is typically
used for open approaches. The techniques of robotic
tongue base resection and robotic radical tonsillectomy
have been well described6.
Larynx and HypopharynxLarynx and hypopharynx surgeries encompasses both
benign vocal fold pathologies and neoplasms, the surgical
approaches vary from radical open surgery as total
laryngectomy to open partial laryngectomies and
microsurgical techniques. The microsurgery of the larynx
is performed via a narrow field approach due to the use of
tube-shaped laryngoscopes. This narrow field approach
has numerous technical limitations based on the physical
properties of the laryngoscope and the distance created
from the surgeon’s hand to the endolarynx. In addition,
when performed in conjunction with an operating
microscope, the field of view is also limited by the size
and position of the laryngoscope. As the microscope is
positioned ‘‘outside the patient,’’ the operative field is
static and dependent on a straight line of site between the
lens of the microscope and the tissues at the surgical site,
which are over 12 inches apart. The final surgical limitation,
which is inherent in standard microlaryngoscopy is thelong distance between the surgeon’s hands and the
working ends of the instruments. These limitations, which
are inherent in both endoscopic and laparoscopic surgery,
have been found to negatively impact the learning curve
for novice surgeons. The feasibility of TORS was
demonstrated in both the mannequin and the cadaver
models, as well as in the canine model 3,4,11. Among the
advantages noted in the robotic supraglottic resections
were: wide exposure with oral mouth gag system and no
laryngoscope, multiplanar transection of tissues, and a
three-dimensional view provided by the integrated high-
resolution endoscope. Furthermore, the surgeon mayrepeatedly and instantaneously reposition the robotically
controlled endoscope and instruments to change viewpoint
during the procedure rather than reposition a laryngoscope
or microscope to change the view.
Parapharyngeal SpaceThe neoplasms of the parapharyngeal space and
infratemporal fossa in the majority of cases use a cervical,
transparotid, approach that may be associated with
mandibulotomy and the related postoperatory problems in
cosmesis, mastication and swallowing disorders. TORS
holds potential for parapharyngeal and infratemporal fossa
neoplasms as the 30° angled high- magnification
3-dimensional camera optics permitted tremendous
visualization, which then allowed careful identification
and dissection of the carotid artery, jugular vein, andcranial nerves to their entry points at the middle skull
base. With respect to technical limitations and challenges
for this TORS approach, the bony skull base cannot be
resected, and intracranial work cannot be performed given
the technical limitations of the existing robotic instruments
and lack of robotic drills and burrs. Also, dissection below
the level of the carotid artery bifurcation cannot be readily
performed; thus, a transoral formal neck dissection for
cervical metastases is not presently feasible. Subsequent
to the preclinical investigations, we have demonstrated the
successful application of TORS to the skull base in a
human patient with a parapharyngeal to infratemporal
fossa benign cystic neoplasm12.
NasopharynxThe nasopharynx is one of the most challenging areas of
the head and neck to reach and resect. For this reason, the
nasopharynx had been thought of as an inoperable site in
the past. Approaches described in the last few decades
were complicated, with high morbidity13,14. Very recently,
a few case series with a limited number of patients showed
the feasibility of minimally invasive endoscopic approaches
for nasopharyngectomy15. Recently the use of transoral
robotic assisted surgery for nasopharyngeal approaches
has been described in a cadaveric model16.
Skull BaseTransnasal endoscopic techniques have been increasingly
used for surgical access and treatment of neoplastic and
nonneoplastic lesions of the anterior and central skull
base. The increasing popularity of these endoscopic skull
base approaches may be attributed to a larger trend toward
more minimally invasive techniques across all surgical
disciplines. The main advantage of transnasal endoscopic
skull base approaches is providing more direct access to
the anterior and central skull base while avoiding
craniofacial incisions and extensive bone removalcommonly used in open surgical approaches. Also, the
wider angle of vision and angled lenses increases the
range of the endoscopic visual surgical field compared
with the “line of sight” visual field gained by surgical
loupes or microscopes. One major disadvantage of
transnasal endoscopic approaches is the inability to provide
watertight dural closure and reconstruction. Current
techniques of endoscopic skull base reconstruction, such
as tissue grafts, mucosal flaps provides reconstruction of
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limited skull base defects17. The difficulty to secures large
dural deffects led to the exploration of the feasibility of
robotic-assisted endoscopic surgery and repair of the
anterior and central skull base. The preclinical studies
showed that further instrument development and continued
investigation are warranted before this approach can be
touted as an exciting alternative to present surgicaltechniques and standard approaches12,18.
Neck SurgeryNeck surgeries encompass salivary glands resections, neck
dissections, congenital cysts and thyroid and parathyroid
surgery among others. Currently, patients are much more
interested not only in treatment of the disease but also in
postoperative quality of life, which includes such
considerations as operative scar, degree of pain, and ability to
return rapidly to the work. These interests have focused on
the cosmetic result and the noninvasiveness of the operation,
resulting in the development of minimally invasive surgical
techniques. Since the first report of endoscopic parathyroid
surgeries in 199619, various techniques of endoscopic thyroid
surgery have been introduced during the past decade20,21.
Recently, different services of head and neck worldwide
reported robot-assisted thyroid and others neck surgeries, in
order to diminish the scars in the neck and to avoid the
common complications of the traditional approaches22-24.
The follow-up results and the morbidity outcomes need
further evaluation, in addition the reproducibility of the
different techniques described must also be confirmed by
numerous teams prior to adoption of these techniques.
Final CommentsRobotic-assisted head and neck surgery provides high-
magnification and three-dimensional optics that allows
careful dissection, with en bloc resection, allnd allows for
identification of nerves and vessels before transection or
inadvertent injury. Hemostasis is achieved with either
monopolar or bipolar cautery robotic instrumentation and
the use of small-sized hemoclips. The robotic
instrumentation furthermore offers at least 360 degrees of
freedom of movement, varied levels of scaled movement,
and hand tremor buffering that greatly enhances the
precision by which the procedures can be performed.
Robotic-assisted head and neck surgery provides technicalfeasibility of accessing and performing resections without
requiring transcervical or transmandibular approaches.
Robotic surgery in the head and neck region holds promise
for human clinical application and may prove valuable as
a minimally invasive and low morbidity primary therapy
for varied benign and malignant head and neck lesions. In
some anatomic sites may also shift the paradigm back to
primary surgery with or without radiation for the
management of head and neck cancers.
Bibliography1 Dasgupta P, Patil K, Anderson C, Kirby R. Transition from open to
robotic-assisted radical prostatectomy. BJU Int. 2008;101(6):667-668.
2 Reiter D. Complications of mandibulotomy. Otolaryngol Head NeckSurg. 2004; 131(3):339.
3 Weinstein GS, O’Malley BW Jr, Hockstein NG. Transoral robotic surgery: supraglottic laryngectomy in a canine model. Laryngoscope.
2005;115(7):1315-1319.4 Hockstein NG, Nolan JP, O’Malley BW Jr, Woo YJ. Robot-assisted
pharyngeal and laryngeal microsurgery: results of robotic cadaverdissections. Laryngoscope. 2005;115(6):1003-1008.
5 O’Malley BW Jr, Weinstein GS, Snyder W, Hockstein NG. Transoralrobotic surgery (TORS) for base of tongue neoplasms. Laryngoscope.2006;116(8):1465-1472.
6 Weinstein GS, O’Malley BW Jr, Snyder W, Sherman E, Quon H.
Transoral robotic surgery: radical tonsillectomy. Arch OtolaryngolHead Neck Surg. 2007;133(12):1220-1226.
7 Weinstein GS, O’Malley BW Jr, Snyder W, Hockstein NG. Transoralrobotic surgery: supraglottic partial laryngectomy. Ann Otol RhinolLaryngol. 2007;116(1):19-23.
8 Koch WM. Head and neck surgery in the era of organ preservationtherapy. Semin Oncol 2000;27(4 Suppl 8):5–12.
9 Harrison LB, Zelefsky MJ, Armstrong JG, et al. Performance statusafter treatment for squamous cell cancer of the base of tongue-acomparison of primary radiation therapy versus primary surgery. Int J Radiat Oncol Biol Phys 1994; 30:953–957.
10 Nasri S, Oh Y, Calcaterra TC. Transpharyngeal approach to base oftongue tumors: a comparative study. Laryngoscope 1996;106:945–950.
11 Hockstein NG, Nolan P, O’Malley BW Jr, Woo YJ. Roboticmicrolaryngeal surgery: a technical feasibility study using thedaVinci“ surgical robot and an airway mannequin. Laryngoscope.2005;115:780–785.
12 O’Malley BW Jr, Weinstein GS. Robotic skull base surgery: preclinical investigation to human clinical application. ArchOtolaryngol Head Neck Surg. 2007;133(12):1215-1219.
13 Shu C-H, Cheng H, Lirny J-F, et al. Salvage surgery for recurrentnasopharyngeal carcinoma. Laryngoscope 2000; 110:1483–1488.
14 Wei WI, Lam KH, Sham JS. New approach to the nasopharynx: themaxillary swing approach. Head Neck 1991;13: 200 –207.
15 Chen MK, Lai JC, Chang CC, Liu MT. Minimally invasive endoscopicnasopharyngectomy in the treatment of recurrent T1–2a nasopharyngealcarcinoma. Laryngoscope 2007;117:894 – 896.
16 Ozer E, Waltonen J. Transoral Robotic Nasopharyngectomy: a novelapproach for nasopharyngeal lesions. Laryngoscope 2008;118:1613-1616.
17 Kassam A, Carrau RL, Snyderman CH, Gardner P, Mintz A.
Evolution of reconstructive techniques following endoscopicexpanded endonasal approaches. Neurosurg Focus. 2005;19(1):E8.
18 Hanna EY, Holsinger C, DeMonte F, Kupferman M. Roboticendoscopic surgery of the skull base: a novel surgical approach.Arch Otolaryngol Head Neck Surg. 2007;133(12):1209-1214
19 Gagner M. Endoscopic subtotal parathyroidectomy in patients with primary hyperparathyroidism. 1996; Br J Surg 83:875.
20 Miccoli P, Berti P, Bendinelli C, Conte M, Fasolini F, Martino E. Minimally invasive video-assisted surgery of the thyroid: a preliminary report. Langenbecks Arch Surg 2000;385:261–264.
21 Gagner M, Inabnet WB III. Endoscopic thyroidectomy for solitarythyroid nodules. Thyroid 11:161–163
22 Kang SW, Jeon JJ, Yun JS, et al. Robot assisted endoscopic surgery for thyroid cancer: experience with the first 100 patients. SurgEndosc 2009(1).
23 Lobe TE, Wright SK, Irish MS. Novel uses of surgical robotics inhead and neck surgery.J Laparoendosc Adv Surg Tech 2005;15(6)647-652.
24 Haus BM, Kambham N, Le D, et al. Surgical robotics applicationsin otolaryngology. Laryngoscope 2003; 113:1139-1144.
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AbstractThe incidence of head and neck melanoma has steadily
risen over the past thirty years. Local and regional
disease control remains the critical determinant of head
and neck melanoma outcomes, and therefore surgery
remains the key treatment modality for malignant
melanoma of the head and neck. Multi-center, prospective
studies have redefined the surgical decision making in
regards to the extent of surgical margins and the critical
role of sentinel lymph node biopsy. Furthermore, newer
technologies in sentinel node localization and adjuvant
therapies have aided the prognosis, management, and
treatment of head and neck melanoma. These advances
have improved the ability of head and neck surgeons to
maximize loco-regional disease control by optimal and
thoughtful surgical planning.
IntroductionThe incidence of malignant melanoma is increasing at a
rapid rate. The National Cancer Institute’s SEER data has
tracked the steady increase in melanoma incidence in the
United States from 7.9 to 21.1 per 100,000 over the past
thirty years. Mortality rates, in contrast, have remainedrelatively stable at 2.7 per 100,0001. In this same time
frame, the management of melanoma has undergone
significant changes and improvements. In this review, we
address the current management of head and neck
malignant melanoma and summarize the key clinical
research which has established the rationale for surgical
margins, sentinel lymph node biopsy, technological
advances in sentinel lymph node localization, and use of
radiation therapy for head and neck melanoma.
Surgical Margins for PrimaryMelanoma ExcisionComplete surgical excision has been and remains the
treatment standard of care for primary melanoma. The
rationale for the size of the surgical margins is based on
melanoma’s ability to migrate from primary tumors
through cutaneous lymphatics to regional lymph nodes.
Traditionally, larger margins of surgical excision were
advocated as a means to prevent lymphatic spread. The
concept of 5 cm margins was challenged by Breslow and
Macht2, and subsequent randomized, prospective trials
demonstrated that narrower margins were, indeed, equally
curative.
Three landmark prospective, randomized studies
established the extent of margins necessary to control
local disease and constitute the current surgical treatment
paradigm. Veronesi et al. in a multi-center international
trial compared 1cm and 3cm margins for thin melanoma
measuring up to 2 mm Breslow depth3, 4. They demonstrated
in their primary report and in their subsequent publication
that the there was no statistically significant difference
between the narrower margin and the wider margin in
local recurrence rates (LRR), disease free survival (DFS)and overall survival (OS). Unfortunately, Veronesi’s study
did not specifically address nor did it include head and
neck melanoma subjects. The subsequent study, by Balch
et al., included a patient population of trunk, extremity,
and head and neck melanoma, but it addressed intermediate
size lesions, specifically Breslow depths of 1-4 mm5, 6.
Their data also did not demonstrate any statistical
difference between OS and LRR, thus establishing a
recommendation for 2cm margins for intermediate size
Head and Neck Melanoma:Current Surgical PracticesZvonimir L. Milas, MD and Randal S. Weber, MD
Department of Head and Neck Surgery
MD Anderson Cancer Institute
Correspondence:
Randal S. Weber, MD
Professor and Chairman, Department of Head & Neck Surgery
1515 Holcombe Blvd., Unit 1445, Houston, Texas 77030-4009
Phone: (713) 745-0497
Fax: (713) 794-4662
Email: rsweber@mdanderson.org
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lesions. The studies of Veronesi and Balch were validated
by a third prospective randomized study. Ringborg et al
looked at thin and intermediate lesions (0.8 mm to 2 mm)
comparing surgical margins of 2 cm and 5 cm7, 8. Although
no randomized study has prospectively studied margins
necessary for local control in only head and neck
melanomas, the extrapolated data from these studiessupport a 1 cm margin for thin melanomas, up to 1 mm
depth, and a 2 cm margin for intermediate depth lesions.
More recently, the United Kingdom Melanoma Study
group, in a randomized, prospective study, examined
surgical margins necessary for thicker melanomas, greater
than 2 mm Breslow depth9. Their results demonstrated an
increased LRR in patients with 1 cm margins, but no
difference in melanoma specific survival and OS. This UK
study did not include head and neck melanomas nor did it
address differences between 2 and 3 cm margins for
thicker melanomas. Finally, the thickest of melanomas,
>4mm Breslow depth, have not been studied prospectively,
but a retrospective review did not support the use of
surgical margins greater than 2 cm10. While not settled
definitively, thick lesions in head and neck melanoma
patients should be treated with 2 cm margins. Attempting
larger margins in head and neck melanoma frequently is
limited by the proximity of critical facial structures.
Lymph Node InvolvementThe evaluation and treatment of lymph node metastases in
melanoma has evolved significantly over the past 30
years. Therapeutic lymph node dissections (TLND) have
been and remain the standard of care for clinically
involved lymph node basins11. However, there has beendebate about the most appropriate treatment for the
clinically negative nodal basins in melanoma, especially
for intermediate thickness tumors measuring 1 mm to 4
mm. Elective lymph node dissections (ELND) historically
were the standard of treatment for intermediate and thick
melanomas of the head and neck. Yet, multiple trials were
performed in hopes of demonstrating an overall survival
benefit in patients who underwent ELND instead of
observation and TLND for progressive disease12-15. These
studies failed to demonstrate any benefit for patients
undergoing ELND. As a result and prior to the advent of
sentinel lymph node biopsy (SLNB), surgeons trended toobserve the lymph node basins after wide local excision of
intermediate thickness melanomas and reserved TLND for
clinically involved lymph node basins.
Lymph node status has been recognized as the most important
prognostic factor of survival for melanoma12, 16-18. Morton’s
landmark study discussed SLNB as a method of identifying
risk of lymph nodal involvement by tumor19. SLNB in
head and neck melanoma quickly replaced prior strategies
as the standard of care for nodal basin evaluation and
treatment. Indeed, 15-20% of patients diagnosed with
head and neck melanoma will present initially with nodal
metastasis 20-22. Thus, SLNB identifies the subpopulation
of microscopic nodal positive patients while shielding the
remaining 80-85% nodal negative patients from a larger
staging surgery, ELND. Appropriate patient selection,however, for SLNB is critical for accurate application of
prognostic data. Thus, patients with positive nodal basins
or distant metastases and patients with altered lymphatic
drainage from prior surgery, neck dissections, or radiation
do not benefit from SLNB.
The most convincing prospective, randomized trial
published to date on the role of SLNB for melanoma is the
Multi-center Selective Lymphadenectomy Trial I (MSLT-I)23.
Morton et al compared wide local excision and observation
with subsequent lymphadenectomy (TLND) for clinically
positive lymph node involvement to wide local excision
and SLNB with completion lymphadenectomy (CLND)
for positive SLNB in intermediate thickness melanomas.
This study confirmed the prognostic role of SLNB, but it
also demonstrated a clinical advantage of DFS after
SLNB. While there was no OS difference, the 5 year DFS
rates were significantly higher in the SLNB group in
comparison to the observation group, 78.3% vs. 71.3%
respectively. The primary utility of SLNB is as a
prognosticator of outcomes, as evidenced by the higher
5-year survival rates of patients with negative SLNs
(90.2%) in contrast to those with positive SLNs (72.3%;
P < .001). Most importantly, MSLT-1 demonstrated a
survival advantage between immediate lymphadenectomyin patients with subclinical sentinel-node metastases
(72.3%) and patients with delayed lymphadenectomy for
clinically detected nodal relapse. (52.4%; P = 0.004)23.
Thus, SLNB is critical for staging and prognostic value in
patients with intermediate-thickness melanoma, and has
survival advantage in patients with positive SLNB who
undergo immediate completion lymphadenectomy.
Technical Considerations of Sentinel LymphNode BiopsySLNB, however, is not without its challenges. Nuclear
medicine imaging provides a lymphoscintigraphic mapwhich is used preoperatively for surgical planning.
However, the complex and rich lymphatic drainage of the
head and neck region can obscure accurate identification
of the true SLN. Indeed, head and neck melanomas
frequently are mapped to multiple lymph node basins with
multiple lymph nodes identified in each basin20, 24. This
fact may explain the higher rate of false negative SLNB in
head and neck melanoma in comparison to truncal and
extremity melanoma20. Imaging by planar
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lymphoscintigraphy is also limited by the complexity of
the lymphatic drainage of the head and neck. Because of
the smaller size of the lymph nodes and their close
proximity in a compressed space, multiple lymph nodes
are potentially indistinguishable on preoperative imaging,
leading to possible surgical sampling error25,26.
Furthermore, the primary tumor and the injected tracermay be in very close proximity to the SLN. The signal
from the tracer injection can completely obscure the true
SLN, thus leading to a false negative biopsy of a secondary
draining lymph node26. Finally, conventional planar
lymphoscintigraphy, especially in the head and neck, is
limited by the lack of anatomic references26.
In contrast, the hybrid single photon emission computed
tomography camera with integrated computed tomography
(SPECT/CT) combines tomographic lymphoscintigrams
with CT images and has only recently been developed.
This combined imaging modality has a significant
advantage of demonstrating an anatomical relationship
between the SLN and the surrounding structures27. SPECT/
CT also can detect additional drainage basins and improved
anatomical localization, especially in patients with
inconclusive conventional lymphoscintigrams26, 27. This
technology has not changed the indications for and
benefits derived from SLB, but it has certainly improved
the peri-operative planning required for a successful SLB.
Ultimately, more experience needs to be accumulated and
reviewed in order to confirm the initial impressions that
SPECT/CT imaging enhances surgical exploration and
may improve melanoma staging with a decrease in false
negative rates.
The Role of Radiation Therapy in MelanomaMelanoma has been generally perceived as radio-resistant
tumor, thus external beam radiotherapy as adjunctive
treatment never came to widespread use for melanoma28.
The clinical efficacy and postoperative use of radiation
therapy has been widely debated and remains controversial14.
Furthermore, postoperative adjuvant radiation therapy has
not been shown to prolong survival29. The rationale,
however, for adjuvant radiation therapy in melanoma is
based on the reduction and control of residual microscopic
disease, thereby reducing the morbidity caused by regionalrecurrences and risk reduction associated with repeat
surgical procedures30, 31. Retrospective studies examining
the pattern and frequency of regional lymph node
recurrence have identified certain clinical and pathologic
features which increase loco-regional recurrence rates.
Lymph node extra-capsular spread, large number nodal
disease, and/or large volume nodal disease have been
associated with significantly increased regional
recurrences32-34. Consequently, multiple retrospective
studies have attempted to address the benefit of
postoperative radiotherapy for patients with such clinical
and pathologic characteristics predisposing to regional
recurrence.
Many authors have demonstrated regional control rates of
90% and greater with postoperative radiation therapy afterwide local excision and lymphadenectomy35-38. These
regimens use mostly large dose, hypofractionated radiation.
Patients with significant co-morbid conditions or
contraindications to TLND benefit from elective radiation
therapy. Indeed, Ballo et al achieved a 93% regional
control rate with a 5.3 year follow-up using a
hypofractionated regimen in patients with significant
co-morbid conditions who had excision of primary tumor
and palpable nodal disease, but not TLND38. Yet, other
authors do not support the use of postoperative adjunctive
radiotherapy because their reported regional recurrence
rates are essentially unchanged in comparison to only
surgical treatment34, 39. Certainly, there is no argument that
surgical management is the standard of care for cervical
node metastases from metastatic melanoma. At our
institution, we believe there is sufficient evidence of loco-
regional control to recommend radiation therapy to patients
with bulky nodal tumor involvement, extracapsular nodal
involvement, or significant co-morbidities.
SummaryAlthough there have been significant advances in
chemotherapy and immunotherapy, loco-regional control
remains the critical determinant of head and neck
melanoma outcomes. Consequently, surgery remains thekey treatment modality for melanoma, and the role of head
and neck surgeons is to maximize loco-regional disease
control by optimal and thoughtful surgical planning.
Innovative strategies such as SLNB and contributions
from multidisciplinary efforts have aided the prognosis,
management, and treatment of head and neck melanoma.
Most importantly, new knowledge from large, multi-
institutional studies has in the past and continues to refine
our understanding and management of head and neck
melanoma.
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2. Breslow A, Macht SD. O ptimal s ize of resection margin for th incutaneous melanoma. Surg Gynecol Obstet. Nov 1977;145(5):691-692.
3. Veronesi U, Cascinelli N. Narrow excision (1-cm margin). A safeprocedure for thin cutaneous melanoma. Arch Surg. Apr1991;126(4):438-441.
4. Veronesi U, Cascinelli N, Adamus J, et al. Thin stage I primarycutaneous malignant melanoma. Comparison of excision with marginsof 1 or 3 cm. N Engl J Med. May 5 1988;318(18):1159-1162.
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6. Balch CM, Urist MM, Karakousis CP, et al. Efficacy of 2-cm surgical margins for intermediate-thickness melanomas (1 to 4 mm). Results of a multi-institutional randomized surgical trial. Ann Surg.Sep 1993;218(3):262-267; discussion 267-269.
7. Ringborg U, Andersson R, Eldh J, et al. Resection margins of 2versus 5 cm for cutaneous malignant melanoma with a tumorthickness of 0.8 to 2.0 mm: randomized study by the Swedish Melanoma Study Group. Cancer. May 1 1996;77(9):1809-1814.
8. Cohn-Cedermark G, Rutqvist LE, Andersson R, et al. Long termresults of a randomized study by the Swedish Melanoma StudyGroup on 2-cm versus 5-cm resection margins for patients withcutaneous melanoma with a tumor thickness of 0.8-2.0 mm. Cancer.Oct 1 2000;89(7):1495-1501.
9. Thomas JM, Newton-Bishop J, A'Hern R, et al. Excision margins inhigh-risk malignant melanoma. N Engl J Med. Feb 192004;350(8):757-766.
10. Heaton KM, Sussman JJ, Gershenwald JE, et al. Surgical marginsand prognostic factors in patients with thick (>4mm) primarymelanoma. Ann Surg Oncol. Jun 1998;5(4):322-328.
11. Schmalbach CE, Johnson TM, Bradford CR. The management ofhead and neck melanoma. Curr Probl Surg. Nov 2006;43(11):781-
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13. Cascinelli N, Morabito A, Santinami M, MacKie RM, Belli F.
Immediate or delayed dissection of regional nodes in patients withmelanoma of the trunk: a randomised trial. WHO MelanomaProgramme. Lancet. Mar 14 1998;351(9105):793-796.
14. Mack LA, McKinnon JG. Controversies in the management ofmetastatic melanoma to regional lymphatic basins. J Surg Oncol. Jul1 2004;86(4):189-199.
15. Sim FH, Taylor WF, Ivins JC, Pritchard DJ, Soule EH. A prospectiverandomized study of the efficacy of routine elective lymphadenectomyin management of malignant melanoma. Preliminary results. Cancer.Mar 1978;41(3):948-956.
16. Cascinelli N, Belli F, Santinami M, et al. Sentinel lymph node biopsyin cutaneous melanoma: the WHO Melanoma Program experience. Ann Surg Oncol. Jul 2000;7(6):469-474.
17. Leong SP, Accortt NA, Essner R, et al. Impact of sentinel node statusand other risk factors on the clinical outcome of head and neckmelanoma patients. Arch Otolaryngol Head Neck Surg. Apr2006;132(4):370-373.
18. Lin D, Franc BL, Kashani-Sabet M, Singer MI. Lymphatic drainage patterns of head and neck cutaneous melanoma observed onlymphoscintigraphy and sentinel lymph node biopsy. Head Neck.Mar 2006;28(3):249-255.
19. Morton DL, Wen DR, Wong JH, et al. Technical details ofintraoperative lymphatic mapping for early stage melanoma. ArchSurg. Apr 1992;127(4):392-399.
20. Chao C, Wong SL, Edwards MJ, et al. Sentinel lymph node biopsy for head and neck melanomas. Ann Surg Oncol. Jan-Feb2003;10(1):21-26.
21. Kane WJ, Yugueros P, Clay RP, Woods JE. Treatment outcome for424 primary cases of clinical I cutaneous malignant melanoma ofthe head and neck. Head Neck. Sep 1997;19(6):457-465.
22. Morton DL, Wen DR, Foshag LJ, Essner R, Cochran A. Intraoperativelymphatic mapping and selective cervical lymphadenectomy forearly-stage melanomas of the head and neck. J Clin Oncol. Sep1993;11(9):1751-1756.
23. Morton DL, Thompson JF, Cochran AJ, et al. Sentinel-node biopsyor nodal observation in melanoma. N Engl J Med. Sep 282006;355(13):1307-1317.
24. Carlson GW, Murray DR, Greenlee R, et al. Management ofmalignant melanoma of the head and neck using dynamiclymphoscintigraphy and gamma probe-guided sentinel lymph nodebiopsy. Arch Otolaryngol Head Neck Surg. Mar 2000;126(3):433-437.
25. Jansen L, Koops HS, Nieweg OE, et al. Sentinel node biopsy formelanoma in the head and neck region. Head Neck. Jan2000;22(1):27-33.
26. Mar MV, Miller SA, Kim EE, Macapinlac HA. Evaluation andlocalization of lymphatic drainage and sentinel lymph nodes in patients with head and neck melanomas by hybrid SPECT/CTlymphoscintigraphic imaging. J Nucl Med Technol. Mar2007;35(1):10-16; quiz 17-20.
27. van der Ploeg IM, Valdes Olmos RA, Kroon BB, et al. The yield ofSPECT/CT for anatomical lymphatic mapping in patients withmelanoma. Ann Surg Oncol. Jun 2009;16(6):1537-1542.
28. Lentsch EJ, Myers JN. Melanoma of the head and neck: currentconcepts in diagnosis and management. Laryngoscope. Jul2001;111(7):1209-1222.
29. Creagan ET, Cupps RE, Ivins JC, et al. Adjuvant radiation therapy for regional nodal metastases from malignant melanoma: arandomized, prospective study. Cancer. Nov 1978;42(5):2206-2210.
30. Ballo MT, Ang KK. Radiotherapy for cutaneous malignantmelanoma: rationale and indications. Oncology (Williston Park).Jan 2004;18(1):99-107; discussion 107-110, 113-104.
31. Mendenhall WM, Amdur RJ, Grobmyer SR, et al. Adjuvantradiotherapy for cutaneous melanoma. Cancer. Mar 152008;112(6):1189-1196.
32. Calabro A, Singletary SE, Balch CM. Patterns of relapse in 1001consecutive patients with melanoma nodal metastases. Arch Surg.Sep 1989;124(9):1051-1055.
33. Lee RJ, Gibbs JF, Proulx GM, Kollmorgen DR, Jia C, Kraybill WG. Nodal basin recurrence following lymph node dissection formelanoma: implications for adjuvant radiotherapy. Int J RadiatOncol Biol Phys. Jan 15 2000;46(2):467-474.
34. Shen P, Wanek LA, Morton DL. Is adjuvant radiotherapy necessaryafter positive lymph node dissection in head and neck melanomas?Ann Surg Oncol. Sep 2000;7(8):554-559; discussion 560-551.
35. Ang KK, Byers RM, Peters LJ, et al. Regional radiotherapy asadjuvant treatment for head and neck malignant melanoma.Preliminary results. Arch Otolaryngol Head Neck Surg. Feb1990;116(2):169-172.
36. Ang KK, Peters LJ, Weber RS, et al. Postoperative radiotherapy forcutaneous melanoma of the head and neck region. Int J Radiat OncolBiol Phys. Nov 15 1994;30(4):795-798.
37. Ballo MT, Ang KK. Radiation therapy for malignant melanoma.Surg Clin North Am. Apr 2003;83(2):323-342.
38. Ballo MT, Ross MI, Cormier JN, et al. Combined-modality therapy for patients with regional nodal metastases from melanoma. Int JRadiat Oncol Biol Phys. Jan 1 2006;64(1):106-113.
39. Moncrieff MD, Martin R, O'Brien CJ, et al. Adjuvant postoperativeradiotherapy to the cervical lymph nodes in cutaneous melanoma: isthere any benefit for high-risk patients? Ann Surg Oncol. Nov2008;15(11):3022-3027.
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Y E A R B O O K 2 0 0 9 V O L U M E 2 N U M B E R 1
IntroductionSquamous cell carcinomas are the most common tumors
of the upper aerodigestive tract. The presence of cervical
lymph node metastases is one of the most important
prognostic factors for patients with head and neck
carcinomas. Lymph node metastases are associated with a
decrease in the survival rate of up to 50% in this patient
group1. Imaging modalities such as ultrasonography,
magnetic resonance imaging (MRI) and positron emission
tomography (PET) have facilitated detection of distant
metastases and can identify suspicious regional nodes, but
they can not identify smallest metastases within these
nodes. Current publications report on a sensitivity rate of
about 70-80% for the detection of cervical metastases by
sonography, magnet resonance imaging (MRI), computed
tomography (CT) and 18F-fluordesoxyglucose (FDG)-positron emission tomography (PET) as well as PET/CT2-6.
The incidence of clinically occult metastases for patients
with carcinomas of the upper aerodigestive tract still
amounts to 20%7-9.
Currently, the extent of neck dissection is based
predominately on histological type, stage of primary
tumor, and the preoperative knowledge of lymph node
involvement. If occult metastases are detected in the neck
specimen, adjuvant radiotherapy will usually be indicated
while in case of a neck without lymph node metastases
there are no therapeutic consequences. Moreover, several
studies have shown that the status of lymph nodes is the
most important prognostic indicator of survival and the
risk of recurrence in patients with clinically involved
lymph nodes. For this reason, removal and histologic
examination of lymph nodes is considered the most
accurate method for assessing spread of disease to the
lymph nodes, offers the ability to optimally plan adjuvant
therapy and seems to be the only effective therapeutic
option for local control and potential cure. The procedure
of neck dissection is associated with a risk for functional
disability and aesthetic deformity after operation10. For
this reason the routine use of neck dissection especially in
cases of N0 neck is discussed.
The Sentinel Node (SN) conceptThe SN concept was first postulated by Gould in 196011
and Cabanas in 197712. In 1990 it was introduced for
diagnosing melanoma lymph node metastases. The
usefulness as a prognostic indicator of metastases in
melanomas led to an expanded application for breast,
colon, gastric, thyroid, oesophageal, lung as well as head
and neck cancer. Since 1996 trials studying SN biopsy in
HNSCC were initiated, primarily analyzing oral cancer as
it is the most accessible mucosal site. The place of SN
biopsy in staging and management of HNSCC is still anongoing debate. Until now it has not achieved the status of
standard of care for the treatment of HNSCC patients.
However, a large number of studies have been published
in the literature on different aspects of this technique.
The concept of SN biopsy is based on the fact that the first
lymph node in a lymphatic chain (the sentinel node) will
be the first affected by metastasis and that metastases only
subsequently travel to the remaining regional lymph
nodes. Therefore, if the sentinel node can be shown to be
negative, it is highly unlikely that other lymph nodes are
affected.
The lymphatic mapping is done by passage of a marking
dye or radioactive substance, injected by a tumoral or
peritumoral injection. Several techniques have been
reported to identify the sentinel nodes. When a
radiotracer is injected at several sites around the tumor
the location of SN is depicted by a gamma camera in
the department of nuclear medicine or by a gamma
probe in the operation room.
Sentinel Node in Head and Neck CancerSusanne Wiegand, Jochen A. Werner
Department of Otolaryngology, Head and Neck Surgery, UKGM, Marburg, Germany
Correspondence to:
Prof. Dr. J.A. Werner, Department of Otolaryngology, Head and Neck SurgeryUniversity Hospital Giessen & Marburg, Campus Marburg. Deutschhausstr.
335037 Marburg, Germany
Tel: +49-6421-5862888
Fax: +49-6421-5866367
E-mail: wernerj@med.uni-marburg.de
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The problem of blue dye is that it stains the area around
the primary tumor which complicates the resection of the
primary tumor and may alter the absorption of laser
energy which is often used to resect tumors of the upper
aerodigestive tract13. Moreover the blue dye often
extravasates into the tissue14. Therefore most groups
prefer a radioactive tracer without using blue dye.
All methods had reliable results in experienced hands.
Though theoretically the sentinel node should be one
node, in practice there is often more than one lymph node
which is positive by either blue dye method or radiotracer
method and they are labelled as sentinel node. Since most
of the time, there is more than one sentinel node, false
negative rates fall if multiple nodes were removed instead
of one single node.
Therefore one topic that is widely discussed around SN
biopsy is how many lymph nodes should be removed. The
principle of SN biopsy is to find the node into which is the
greatest lymph flow from the tumor. Therefore, the key to
SN mapping is to find the route of lymph flow from the
tumor. One complicating aspect in neck surgery is that the
lymphatic drainage pathways are quite intricate. Therefore
the use of SN biopsy is still debated since there is a
variability of the mucosal lymphatic drainage from
different mucosal sites and the direction of the lymphatic
drainage is not always predictable.
SN in head and neck cancer
Depending on their localization, carcinomas of the upperaerodigestive tract drain to different lymph node levels in
the neck. Oropharyngeal cancer initially metastasizes
most frequently to levels II and III and less frequently to
levels I, IV and V. Levels I-III are at greatest risk for nodal
metastases from carcinomas of the oral cavity. The
metastases of laryngeal and hypopharyngeal tumors are
most often located in level II-IV. Metastases in levels I to
V are rare and usually associated with metastases in lymph
nodes along the jugular vein. The nodes of level VI were
included in tumors of the glottic/subglottic larynx, pyriform
fossa apex and the postcricoid region.
The advantages of SN may are a more accurate loco-
regional lymph node staging and an identification of
lymph node metastases outside the typical metastatic
pattern allowing for a more accurate planning of surgical
excision. This approach will avoid the morbidity associated
with a more extensive neck dissection for HNSCC
patients. Sentinel Node biopsy offers the chance to stage
the neck with less morbidity than a selective neck
dissection. The failure rate of selective neck dissection is
between 1.9% and 5%. Common complications and
morbidities after neck dissection include numbness and/or
burning sensation in parts of the neck or ear, neck pain,
shoulder discomfort, lymphedema, neck tightness, and
aesthetic disfigurement.
The aim of SN biopsy is to preserve the quality of lifewithout risking the oncologic result. Analyzing the quality
of life after sentinel node biopsy and selective neck
dissection it could be shown that the functional outcome
after sentinel node biopsy is significantly better15.
Performing a metaanalysis Paleri et al.16 showed that the
cumulative payoff for the sentinel node biopsy arm was
lower than that for the elective neck dissection arm by
about 1%. However, the problem is that a tumor in the
head and neck region will eventually show more than one
isolated lymph node17.
If several lymph nodes have to be removed, the advantage
of SN biopsy over selective neck dissection is questionable.
Especially the biopsy of multiple sentinel nodes in two or
more levels seems to offer only few advantages over
selective neck dissection for patients with HNSCC. Dünne
et al.18 defined SN as the most radioactive lymph nodes
identified by gamma probe and 1-3 SN per patient were
removed. One single SN was removed by Stoeckli et al.19.
They used dynamic lymphoscintigraphy to identify the
lymph node which was first affected by the radiotracer. In
most studies between 0-6 SNs were removed. Anuli et
al.20 analyzed how many lymph nodes should be harvested
to accurately stage the neck. They contributed that all
patients would have been staged accurately if only thehottest three nodes had been retrieved. These results stress
that several lymph node have to be resected to avoid false-
negative results21. Remembering that lymphatic structures
are very dense in the head and neck area and altogether
about 300 lymph nodes a
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